1. Field of the Invention
The invention relates to methods and devices for introducing ions into a measuring cell of a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS), in particular for reducing the magnetron orbit of ions introduced into the ICR cell.
2. Description of the Related Art
In a magnetic field with the flux density B, an ion with the mass m, the elementary charge e and the charge number z performs a circular motion (cyclotron motion) in the radial plane perpendicular to the magnetic field lines with the well-known cyclotron frequency:
                              v          c                =                  zeB                      2            ⁢            π            ⁢                                                  ⁢            m                                              (        1        )            The cyclotron radius rc of an ion with the mass m, the elementary charge e, the charge number z, and the kinetic energy Ekin in a magnetic field of the flux density B is given by the following equation:
                              r          c                =                                            2              ⁢                              mE                kin                                              zeB                                    (        2        )            In the thermal energy range, e.g., at a temperature of 298 K, and in a magnetic field with the flux density of 7 Tesla, the cyclotron radius of a singly charged ion with mass 1,000 Dalton is approximately a tenth of a millimeter.
The magnetic field can only trap ions in the plane perpendicular to the magnetic field lines. To prevent the ions from escaping in the axial direction, an electric trapping field is required, which can be generated, e.g., in a cylindrical ICR cell. A simple conventional cylindrical ICR cell contains, axially, at both ends of the cell, end electrodes (or end plates), on which a relatively low DC voltage (normally, 1-2 volts) is applied. The polarity of this DC voltage is the same as the ions to be trapped. The cylinder mantle electrodes of such a simple ICR cell are grounded, thus, an electric trapping field is formed in the ICR cell between the end electrodes and the cylinder mantle. Ions with the mass m and the charge number z oscillate axially in the ICR cell of the length a between the two end electrodes with a trapping frequency νT if a trapping voltage VT is applied:
                              v          T                =                              1                          2              ⁢              π                                ⁢                                                    2                ⁢                α                ⁢                                                                  ⁢                                  zeV                  T                                                            ma                2                                                                        (        3        )            Here e is the elementary charge, and α a constant depending on the ICR cell geometry. With this additional oscillation the ion performs a combination of three independent periodic motions in the ICR cell: cyclotron and magnetron motions in the radial plane, and the trapping oscillations in the axial direction.
In the presence of a trapping field, the frequency measured at the detection electrodes of the ICR cell is no longer the unperturbed cyclotron frequency νc but the reduced cyclotron frequency νR:
                                          v            R                    =                                                    v                c                            2                        +                                                                                v                    c                    2                                    4                                -                                                      v                    T                    2                                    2                                                                    ,                            (        4        )            which is smaller by a magnetron frequency νM than the unperturbed cyclotron frequency:νR=νc−νM  (5)The magnetron frequency of an ion of cyclotron frequency νc and a trapping frequency νT is:
                              v          M                =                                            v              c                        2                    -                                                                      v                  c                  2                                4                            -                                                v                  T                  2                                2                                                                        (        6        )            
FIG. 1 shows the combined motion of an ion in an ICR cell in the magnetic field of the flux density B (1). The combination of the reduced cyclotron motion (2), the trapping oscillation (3), of which the sinusoidal curve is shown in dashed lines (4), and the magnetron motion (5) produces the complicated resulting motion (6) of the ion around the electric field axis (7).
When an ion is axially introduced exactly in the middle of the ICR cell, it will not experience any electric field component perpendicular to its path. The radial components of the electric trapping field are distributed symmetrically around the axis of the DC electric field, i.e. around the axis of the ICR cell. Thus, there is no perpendicular electric field component on the cell axis. However, an ion which is not introduced on axis into the ICR cell experiences a perpendicular electric field component, and the influence of the E×B fields immediately diverts it from its initial path. The ion now drifts perpendicular to both the magnetic field and that radial electric field component into the third dimension and starts an epicycloidal orbit that winds on a circle around the electric field axis. This is a magnetron orbit around the cell axis.
Although the applied electric trapping field helps keeping the ions from escaping the ICR cell, it definitely deteriorates the conditions for a clean measurement of the cyclotron frequency. Due to the radial components of the electric trapping field, the ions do not only circle on their pure cyclotron orbits. As a superimposed motion they follow epicycloidal magnetron orbits and they additionally oscillate in the axial direction with the trapping frequency. The magnetron motion is very slow compared to the cyclotron motion. Its frequency only depends on the magnetic field and the electric field. The size (or diameter) of the initial magnetron orbits of ions in the ICR cell right after they are captured depends on how the ions are transferred to the ICR cell, e.g., whether they are transferred by an electrostatic ion transfer optics or by an RF-multipole transfer optics, or whether or not they are captured using an electric field pulse (“sidekick”) orthogonal to their path and to the magnetic field etc.
Normally, the ICR cell contains a large number of ions, and their masses can be quite different. Before detection, the reduced cyclotron motion of the ions is excited by an oscillating (RF) electric field with a scanned frequency (“Chirp”). When the frequency of the scanned oscillating field becomes equal to the reduced cyclotron frequency (equation 4), its cyclotron motion gets resonantly excited. Depending on the duration and the amplitude of the oscillating (RF) electric field, ions become accelerated and move to larger (excited) cyclotron orbits. This resonant excitation also forces ions with the same charge number-related mass (m/z), which initially circle randomly on small cyclotron orbits having completely different phases, to a coherent motion. At the end of the excitation process ions with the same charge number-related mass (m/z) form a cloud in which these ions move in phase. Coherently moving ions in the cloud induce image charges at the detection electrodes that oscillate with the same frequency and with the same phase. Such oscillating image charges (image currents) generated by all ion clouds are detected, amplified, and after Fourier transformation displayed as a frequency spectrum or, when a frequency to mass mapping (calibration) exists, as a mass spectrum.
One intrinsic property of the (fast) Fourier transform detection method is the appearance of higher harmonic frequencies for each fundamental frequency signal in the frequency spectrum. In the ideal case of a perfectly symmetric electric field, and if the ions are injected in the middle into the ICR cell, only odd-numbered harmonic frequencies should appear in the spectrum due to a pure cyclotron motion around the center of the ICR cell. The intensities and distribution of the odd-numbered harmonics depend on the ion cyclotron radius and the arrangement of the detection electrodes. Any distortion/asymmetry of the electric field or improper injection of an ion packet into the ICR cell, however, entails a magnetron motion of the ions in the ICR cell. In such case, additional even-numbered harmonic frequencies of the main or fundamental ion signal appear in the spectrum.
A large magnetron orbit of ions captured in an ICR cell (negatively) influences the cyclotron excitation process of the ions and their detection. It also impairs the detected signal, leads to an increase of the intensity of the peaks associated with the even-numbered (e.g., second) harmonics in the Fourier transformed spectrum and to more abundant sidebands of the ion signal. In extreme cases, ions can be lost during the cyclotron excitation when they are on large magnetron orbits that are critically close to the cylinder mantle electrodes.
Additionally, a large magnetron orbit can cause problems when using a so-called multiple frequency detection method. Multiple frequency detection multiplies the resolving power of the detected mass peaks. In an ICR cell multiple frequency signals can be obtained if more than two detection electrodes (e.g., 4, 8, etc.) are used. However, this method can only be successfully applied if ions have no magnetron orbits or if they are vanishingly small. Moderate or large magnetron orbits severely complicate the ICR mass spectra and reduce the signal intensity of the multiple-frequency mass peaks.
The as yet unpublished U.S. patent application Ser. No. 13/767,595 of G. Baykut, J. Friedrich, R. Jertz, and C. Kriete, the content of which is herewith incorporated by reference in its entirety, relates to a method for detecting position (center) and size of the initial magnetron orbit of ions captured in an ICR cell. In this method, parameters indicative of position and size of the magnetron motion for an ion with a reduced cyclotron frequency νR in the ICR cell are determined by monitoring relative intensities (relative to the intensity of the main or fundamental peak with frequency νR) of at least one of the ion signals with frequencies of (2nνR±mνM), n=1, 2, 3, . . . , and m=0, 1, 2, 3, 4, . . . , as a function of the time delay between ion injection and cyclotron excitation (post capture delay, PCD), and by evaluating maxima and minima of the relative intensities. The ± sign indicates that either a satellite peak being shifted to higher frequencies or to lower frequencies can be monitored wherein two or more of these satellite peaks can be monitored.
U.S. patent application Ser. No. 13/767,595 also teaches that, if the cyclotron excitation is initiated at a selected PCD time, the magnetron orbit can be reduced, since the PCD time defines the position (=phase) of the ion on its magnetron orbit. At a certain PCD time the cyclotron excitation simultaneously excites the ion's magnetron orbit too, at others the cyclotron excitation leads to reduction of its magnetron orbit. However, reducing the magnetron radius in dependence of the PCD time, which is in some cases quite long, restricts the operations of the FT-ICR mass spectrometer with fast pre-separation techniques, such as a liquid chromatographic separator.
Ions which are generated in external ion sources need to be introduced into the ICR cell for analysis. The pulsed transfer of ions from ion sources or from intermediate ion storage or accumulation devices to the ICR cell includes an extraction and injection event. The flight of the ions to the ICR cell takes an m/z-dependent time (time of flight): When accelerated to the same kinetic energy lighter ions arrive earlier at the ICR cell, heavier ones fly slower and arrive later. Therefore, the extraction and injection pulse defines an injection period Δtin during which all transferred ions enter the ICR cell.
Ions which are generated in external ion sources and which are electrostatically injected into the ICR cell, as the case may be exactly on the cell axis without velocity components perpendicular to the magnetic field, may not be successfully captured in the cell. They can fly through and may exit the ICR cell at the other end. An invention by P. Caravatti (U.S. Pat. No. 4,924,089 A) describes a technique to efficiently capture externally generated ions in the ICR cell. This technique basically uses two fixed electrodes at the ICR cell entrance to apply a transversal electric field during the period of ion introduction. This electric field is perpendicular to the ion path and to the magnetic field, and it tries to divert ions from their path parallel to the magnetic field (“sidekick”). As the ions obtain velocities perpendicular to the magnetic field the Lorentzian force makes them circle on cyclotron orbits, which also lead to magnetron motions due to the radial trapping field components in the ICR cell. In doing so, the simple and straight flight of the ion through the ICR cell and the escape at the other end is effectively avoided.
This method by Caravatti provides the ions introduced into the ICR cell with a velocity component perpendicular to the magnetic field, however there is no complete control over the motion of the ions inside the ICR cell due to following reasons: (i) The transversal electric field effecting the “side-kick” is substantially located outside the ICR cell; and (ii) The ions are “side-kicked” up or down, i.e. along one fixed radial direction, since the two electrodes have fixed configuration. The configuration of the “side-kick” electrodes and the trapping plate near the sidekick electrodes generates an asymmetric electric field which can increase the magnetron motion in the ICR cell.
Another method often used for introducing ions into an ICR cell is the dynamic trapping of ions. In this case, the voltage at the entrance side trapping plate is reduced and the voltage of the other trapping plate is significantly increased. A more complex version of this method is the gas-assisted dynamic trapping of ions. A pulse of collision gas (such as nitrogen or argon) is injected into the cell, which is commonly kept at ultrahigh vacuum, and takes off the excessive kinetic energy and thus reduces the cyclotron orbit size, however on the expense of increasing the magnetron orbit. A quadrupolar excitation of ions in the ICR cell combined with a pulsed collision gas can reduce the magnetron motion. This method makes use of the periodic interconversion of the magnetron and cyclotron motions in the quadrupolar excitation field.
All methods using a pulsed gas have also the disadvantage that the mass spectrometric system is not ready to acquire a highly resolved mass spectrum until the additional gas is substantially pumped away. The continuous application of the pulsed gas method has the further disadvantage of slowly increasing the background pressure.
For an efficient ion injection, the methods described above require a pulsed ion transfer from an external source or from a storage device on the way to the ICR cell. A package of ions is transferred and injected into the ICR cell during a certain time, the injection period Δtin, which is defined by the kinetic energy of the ions and the m/z range of ions of interest. Only during this time period, an electric ion capturing process is applied. If the duration of this capturing process exceeds the actual ion injection period it may lead to loss of ions: In case of the dynamic trapping, the ions of interest could escape the ICR cell if the voltage at the entrance trapping plate is still low. In case of the sidekick method, a permanent application of the sidekick voltages would distort the geometry of the electrical trapping field inside the ICR cell during the ion detection.
Externally generated ions are usually transferred to the ICR cell either using an electrostatic ion transfer system or an RF multipole ion guide. In both of the cases, they may pick up a radial motion in the magnetic fringe fields due to the fact that the ions need to enter a magnetic field during their transfer to the ICR cell. As a consequence, the ions enter the ICR cell with an initial cyclotron motion. The ion injection position at the entrance of the ICR cell could be off the cell axis, which further introduces an initial magnetron motion. Additionally, it is also known that RF multipole ion guides that are used for ion transfer into ICR cells cause a radial displacement of the ion motion during their travel to the ICR cell due to the superposition of the RF electric and magnetic fields. This also leads to an offset ion entrance into the ICR cell and, thus, to an initial magnetron motion.
FIG. 7A shows an example of a dynamically harmonized ICR cell (50), known from the patent application WO 2011/045144 A1 (E. Nikolaev and I. Boldin). This ICR cell has two end electrodes (trapping electrodes 80 and 81), leaf-shaped (e.g., 58) and inverse leaf-shaped (e.g., 55, 57, 59, 61) cylinder mantle electrodes. The leaf-shaped electrodes are connected to ground potential, all inverse leaf plates may be supplied with a common variable DC voltage (DC bias) which normally does not differ too much from the trapping voltage of the end electrodes (80 and 81) of the ICR cell. The reference sign X denotes the cell axis. In order to divide the cell mantle into four equal 90° segments, four of the eight leaf electrodes are longitudinally divided into two halves (e.g. 56a and 56b). Thus the ICR cell has four integral leaf electrodes, four split leaf electrodes, and eight inverse leaf electrodes. The dashed line (10) on the cell indicates the z-position of the cut for the cross-sectional view in FIGS. 7C, 7D, and 7E.
FIG. 7B (prior art) displays the cylinder mantle electrodes open and unwound. There are two excitation segments E consisting of 5 electrodes (60b, 61, 62, 63, 64a) and (69b, 70, 71, 72, 56a). Furthermore, there are two detection segments D consisting of 5 electrodes (56b, 57, 58, 59, 60a) and (65b, 66, 67, 68, 69a). In the detection segments often only the leaf and half leaf electrodes (56b, 58, 60a) and (65b, 67, 69b) are used. The inverse leaf electrodes (57, 59, 66 and 68) are normally not used as detection electrodes since these are connected to DC voltage power supplies and thus lead to noisy ICR signals. However, if the DC voltages are generated by a battery, the noise can be avoided, and all five electrodes in a detection segment can be used for signal detection.
FIG. 7C (prior art) shows a cross sectional view of the dynamically harmonized cell (50) cut at the position indicated by the dashed line (10) in FIG. 7A, including a simplified wiring scheme for the connection of DC bias voltages. Basically, all inverse leaf electrodes can be connected to one single DC voltage source. In this example, instead of one common DC voltage source, four independent DC voltage sources 40, 41, 42, and 43 are used, which may all generate the same DC bias. Each source is connected to a pair of inverse leaf electrodes: The source 41 is connected to electrodes 53 and 55, the source 40 to electrodes 57 and 59, the source 43 to electrodes 61 and 63, the source 42 to electrodes 65 and 67. Individual sources have the advantage of independently varying the DC bias voltages in order to apply a field correction as known from U.S. patent application Ser. No. 13/767,595.
In the dynamically harmonized ICR cell the ions experience a harmonic potential averaged over a cyclotron cycle. The dynamic harmonization is most efficient if the magnetron orbit is small. The invention in U.S. patent application Ser. No. 13/767,595 enables a correction of the offset radial electric field and thus forms an on-axis magnetron motion. Furthermore, it helps reduce the magnetron motion using a post capture delay (PCD). This may introduce extended times for each FT-ICR acquisition which are not appreciated when doing LC-MS. Therefore, large initial magnetron orbits of ions need a more efficient way to be reduced.
In view of the foregoing, an efficient method is needed to quickly introduce and capture external ions in the ICR cell without inducing a large magnetron motion. A new method should be able to efficiently introduce and capture ions in the ICR cell and reduce or minimize their magnetron motions, in the best case even such that the magnetron motions substantially disappear.